Acute effects of beta-blocker with intrinsic sympathomimetic activity on stress-induced cardiac dysfunction in rats

We have reported that α and β adrenergic blockers could protect against emotional stress-induced cardiac dysfunction but those protective effects of β adrenergic blockers with intrinsic sympathomimetic activity (ISA), such as celiprolol, are unknown. The purpose of this study is to evaluate whether ISA could relate with this protective effect.

Rats medicated with celiprolol (8 mg/kg), metoprolol (4 mg/kg), or vehicle, were restrained for 30 min (immobilization stress: IMO) to reproduce emotional stress, and anesthetized to release stress. We measured the fractional area change (FAC) using an echocardiography (SONOS5500) with s12 probe (frequency: 5-12 MHz, frame rate: 120 Hz) at the end of IMO and every 10 min for 1h. During IMO, FAC in rats with a premedication of metoprolol was lower than in those with a premedication of vehicle or celiprolol. At 20 min after IMO, FAC in rats with a premedication of celiprolol was significantly higher than that with a premedication of metoprolol or vehicle (84 ± 9% vs. 65 ± 3% or 60 ± 7%, p<0.05). At 60 min after IMO, FAC in rats with a premedication of vehicle or celiprolol recovered, but FAC in rats with a premedication of metoprolol did not.

Acute premedication with celiprolol could prevent a sudden drop of cardiac function after acute stress such as IMO. ISA might have an important role in preventing stress-induced cardiac dysfunction.